U.S. patent number 4,841,974 [Application Number 07/136,831] was granted by the patent office on 1989-06-27 for apparatus and method for the examination of a liquid medium.
This patent grant is currently assigned to Siemens Aktiengesellschaft. Invention is credited to Walter Gumbrecht, Peter Hobel, Bernhard Montag, Wolfgang Schelter.
United States Patent |
4,841,974 |
Gumbrecht , et al. |
June 27, 1989 |
Apparatus and method for the examination of a liquid medium
Abstract
A measuring canal is provided which is connected to a catheter.
The canal includes a measuring sensor and a reference sensor. The
catheter includes several lumens that have a common opening to the
liquid measuring medium. The flow direction of an infusion solution
at the opening is reversible. A second lumen of the catheter is
connected to the measuring canal which is provided with at least
one measuring sensor and with at least one reference sensor as well
as with a device for setting the outflow of the apparatus to a
predetermined velocity. The flow of an infusion fluid and the
liquid medium alternates in such a fashion that during a first time
interval the measuring sensor is coupled to the liquid medium and
the reference sensor is coupled to the infusion solution. In a
second interval the situation is reversed so that the original
measuring sensor is coupled to the infusion solution and the
original reference sensor is connected to the liquid medium. The
unique arrangement is effective for blood examination. Drift
problems and toxicity problems cannot occur and no electrochemical
reference electrode is required.
Inventors: |
Gumbrecht; Walter (Erlangen,
DE), Schelter; Wolfgang (Uttenreuth, DE),
Montag; Bernhard (Forchheim, DE), Hobel; Peter
(Buckenhof, DE) |
Assignee: |
Siemens Aktiengesellschaft
(Berlin and Munich, DE)
|
Family
ID: |
6316928 |
Appl.
No.: |
07/136,831 |
Filed: |
December 22, 1987 |
Foreign Application Priority Data
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Dec 22, 1986 [DE] |
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3643980 |
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Current U.S.
Class: |
600/348;
204/403.06; 205/778; 205/781.5; 205/782.5; 257/253; 436/68 |
Current CPC
Class: |
A61B
5/14542 (20130101); A61B 5/1473 (20130101); A61B
5/1495 (20130101); G01N 33/49 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); G01N 33/487 (20060101); A61B
005/00 () |
Field of
Search: |
;128/635,632 ;436/68
;204/403,415,416,431,433 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0036171 |
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Sep 1981 |
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EP |
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0120108 |
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Oct 1984 |
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EP |
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0155725 |
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Sep 1985 |
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EP |
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0180662 |
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May 1986 |
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EP |
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3040168 |
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May 1981 |
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DE |
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3038883 |
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Jun 1984 |
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DE |
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Other References
Medical and Biological Engineering Ann. N.Y. Acad. Sc., vol. 87
(1960) pp. 658-668..
|
Primary Examiner: Cohen; Lee S.
Attorney, Agent or Firm: Kenyon & Kenyon
Claims
What we claim is:
1. Apparatus for the examination of a liquid medium to be analyzed,
comprising:
(a) a catheter having a plurality of lumens, each of said lumens
having a common opening to the liquid medium;
(b) means, coupled to a first one of said plurality of lumens, for
providing a reversible flow of an infusion solution, at said
opening, to and from said opening;
(c) a measuring canal coupled to a second one said plurality of
lumens;
(d) means for providing an outflow through said measuring canal at
a predetermined velocity;
(e) at least a first sensor and a second sensor, said measuring
canal connecting said first sensor and said second sensor;
(f) means for measuring differences between outputs of said first
sensor and said second sensor; and
(g) wherein the size of the measuring canal is chosen so that
during a first time interval said first sensor is adjacent to the
infusion solution at the same time that said second sensor is
adjacent to said liquid medium and during a second time interval
said first sensor is adjacent to said liquid medium at the same
time said second sensor is adjacent to said infusion solution.
2. The apparatus of claim 1, wherein said first and second sensors
each comprise an ion-sensitive field effect transistor.
3. The apparatus of claim 2, wherein said field effect transistors
comprise identical membranes.
4. The apparatus according to claim 1 wherein said first and said
second sensors are associated with said measuring canal to form a
common block.
5. The apparatus according to claim 4 wherein said first and second
sensors are integrated together on a common integrated chip.
6. The apparatus according to claim 5, wherein said common
integrated chip further comprises an electronic evaluation circuit
connected to said first and second sensors.
7. The apparatus according to claim 5 wherein said common block
further comprises a cover strip wherein said measuring canal
comprises a groove in said cover strip.
8. The apparatus of claim 5, wherein said common block further
comprises a means for heating said measuring canal.
9. The apparatus of claim 1 further comprising a solution contact
disposed in said measuring canal between said first and second
sensors.
10. The apparatus of claim 1 wherein said means for providing a
reversible flow comprises a reversible pump.
11. The apparatus of claim 1 further comprising a container for the
infusion solution, wherein said means for providing a reversible
flow comprises a pinch valve disposed between said container for
the infusion solution and the catheter.
12. The apparatus of claim 1 wherein each of said plurality of
lumens beyond said first and second lumens is connected to a
further infusion solution.
13. The apparatus of claim 12, wherein at least one of said
plurality of lumens is provided for the measurement of blood
pressure.
14. The apparatus of claim 1 further comprising a plurality of
additional sensors wherein a third sensor is associated with a
fourth sensor and said third and fourth sensors have identical
membranes associated therewith and are connected by said measuring
canal.
15. The apparatus of claim 1 further comprising a plurality of
measuring sensors, and a common reference sensor wherein said
common reference sensor is associated with several measuring
sensors of said plurality of measuring sensors.
16. A method for examining a liquid medium, comprising the steps
of:
a. inserting a catheter, including a plurality of lumens, with a
common opening, into the liquid medium;
b. establishing a flow of liquid through a measuring channel
connected to a first one of said plurality of lumens, said
measuring channel including first and second sensors;
c. feeding an infusion solution through a second one of said lumens
to said common opening;
d. periodically reversing the feeding of said infusion solution to
cause alternate feeding of a first predetermined volume of the
liquid medium and a second predetermined volume of infusion
solution into said measuring channel;
e. setting a rhythm of the periodic reversal to assure that during
a first time interval said liquid medium is adjacent said first
sensor while said infusion solution is adjacent said second sensor
and during a second interval said liquid medium is adjacent said
second sensor while said infusion solution is adjacent said first
sensor; and
f. measuring differences between outputs of said first sensor and
said second sensor.
17. The method of claim 16 further comprising the step of:
g. adjusting the rhythm of the periodic reversal for feeding fluids
to said first lumen so that during a third time interval, between
said first and second time intervals, the first and second sensors
are both coupled to said infusion solution simultaneously.
18. Apparatus for the examination of a liquid medium to be
analyzed, comprising:
(a) a catheter having a plurality of lumens each of said lumens
having a common opening to the liquid medium;
(b) means, coupled to a first one of said plurality of lumens, for
providing a reversible flow of an infusion solution, at said
opening, to and from said opening;
(c) measuring canal coupled to a second one of said plurality of
lumens;
(d) means for providing an outflow through said measuring canal at
a predetermined velocity;
(e) at least a first sensor and a second sensor, said measuring
canal connects said first sensor to said second sensor; and
(f) means for measuring the difference between outputs of the first
sensor and the second sensor;
(g) wherein said means for providing a reversible flow comprises a
reversible pump including a means for controlling the rhythm of
reversing a flow of fluid so that during a first time interval the
liquid medium is adjacent the first sensor while the infusion
solution is adjacent the second sensor and during a second time
interval the infusion solution is adjacent the first sensor while
the liquid medium is adjacent the second sensor.
19. The apparatus of claim 18, wherein each of said plurality of
lumens beyond said first and second lumens is connected to a
further infusion solution.
20. The apparatus of claim 19, wherein at least one of said
plurality of lumens is provided for the measurement of blood
pressure.
Description
BACKGROUND OF THE INVENTION
The invention relates to an apparatus for the examination of a
liquid medium, especially for blood analysis in general and more
particularly to an improved method and apparatus of this type.
Arrangements which include a measuring sensor which is coupled to a
liquid medium to be analyzed as well as to a reference sensor and a
pump, and to a liquid calibrating medium and which also include a
device for measuring any differences between what is detected by
the measuring sensor and what is detected by the reference sensor
are known.
An electro-chemical determination of blood parameters can be
substantially simultaneous to the drawing of blood from a patient
who is to be monitored.
The concentrations of important blood electrolytes, such as calcium
Ca.sup.2+, potassium K.sup.+, and sodium Na.sup.+, or the
concentration of blood gases, for instance, carbon dioxide or
oxygen, or also the pH value or the presence of biomolecules such
as glucose, as well as changes in these concentrations and values
over time, are measured. Calcium controls various biological
processes in the body, for instance, muscle contraction and the
release of hormones. The clinical determination and adjustment of
such concentrations can therefore be of great importance.
An ion-sensitive field effect transistor is suitable as a measuring
sensor. This sensor can be integrated on a silicon chip. A control
electrode serves as a membrane which forms a boundary surface to
the medium to be analyzed. An electrical potential change related
to the concentration to be detected is measured by a shift of ions
at the boundary surface formed by the electrode. This measuring
probe is known as an ISFET or ChemFET. The probe is directly
connected in an alternating fashion to the medium to be analyzed,
and a calibration solution. For purposes of discussion the medium
to be analyzed is considered to be blood.
A valve releases either a stream of blood or the calibration
solution and the released fluid flows through a heat exchanger. The
heat exchanger cools the blood to room temperature. An
electro-chemical reference electrode can be provided as a reference
sensor. It may consist substantially of a metal electrode which is
coated with a hard-to-dissolve salt of the metal. The electrode is
immersed in an electrolyte solution and is closed off by a
diaphragm. The reference sensor is arranged behind the ChemFET, the
measuring probe, in relation to the flow direction of the blood. It
can pptionally also be connected via a bridge electrolyte and a
further diaphragm to the solution under analysis. While such a
measuring arrangement makes possible an on-line measurement of a
solution in an ex vivo arrangement of the sensor, the blood flow in
the feed line hesitates during the calibration. The hesitation of
the flow of the blood necessitates heparinization. In addition, the
entire setup is relatively complicated. (Med. and Biol. Engineering
and Computing, July 1985, pages 329 to 338).
In a further known embodiment of a measuring arrangement for blood
analysis, a ChemFET is provided as a measuring sensor which is
arranged at the end of a catheter at its inside wall. This
measuring sensor is connected via a hose line to an
electro-chemical reference electrode as well as through a
reversible pump to a container that holds a calibration medium. The
reference electrode is connected via a further reversible pump to
an infusion solution or a flushing medium. By the pumps, in
conjunction with valves, blood or the calibration medium or the
flushing medium is alternatingly fed to the measuring sensor. In
this embodiment, the calibration medium, as well as the flushing
medium must be suitable for injection into the blood circulation of
the patient. Interfering potentials can cause a polarization of the
reference electrode and can thereby falsify the result of the
measurement (German Patent No. 30 38 883).
It is furthermore known that in an arrangement for blood
examination, a first ion-sensitive field effect transistor can be
provided as the measuring sensor and another transistor can be
provided as the reference sensor, between which a solution contact
is arranged which is at the null potential of the measuring system.
The measuring section of the device is arranged in a catheter. The
measuring sensor associated with the measuring section is arranged
on the outside of the catheter in the blood stream and remains in
the blood track. In this arrangement, the sensor can be covered up
by resting against the wall of the blood track and the function of
the sensor can thereby be inhibited. Furthermore, the measuring
sensor cannot be flushed, and in addition the presence of the
sensor may cause a rejection reaction by the body which cannot be
prevented. (European Patent OS No. 0 155 725).
A common structural unit can be formed using at least one measuring
sensor, a reference sensor, and a measuring channel. Ion-selective
electrodes of miniaturized design serve as sensors in the common
structural unit design. The measuring channel, connected at one end
to the blood stream via a catheter, is connected at the other end
to a calibration solution via a reversible pump. For calibrating,
the measuring channel is first filled with an infusion solution.
Subsequently, blood is drawn into the measuring channel so as to
bring the measuring electrode into contact with the blood and then,
a different measurement is made. The blood which has been pumped
into the measuring channel for the measurement is subsequently
returned to the blood stream (U.S. Pat. No. 4,535,786).
In this known arrangement a solution under analysis, or also
calibration solutions, which have come into contact with at least
one of the sensors, are therefore returned to the patient. This
means that the membranes of the sensors must therefore be
sterilized. Precautions must be taken against the issuance of toxic
substances from the membranes and, also against any separation or
degradation of the membrane which can lead to the patient suffering
health damage.
It is further known that for the determination of gases,
electrolytes or sugar in the blood, a double-lumen catheter can be
used. One lumen is connected to an electrode chamber. A separate
calibration chamber can be connected to a reversible pump which is
directly connected to the other lumen. In the catheter, there is an
aperture between the two lumens. The electrode chamber contains a
CO.sub.2 or pH electrode, an oxygen electrode and a reference
electrode. A carrier solution is pumped in a closed loop and picks
up gases from the blood through a gas-permeable wall in the
catheter (U.S. Pat. No. 4,221,567).
In a glucose analysis of the blood, a double-lumen needle has
already been used for mixing the sample blood with heparin
solution. This double channel consists of a thin plastic tube which
contains a somewhat shorter inner tube, for removing the
heparinized blood stream. The aperture of the inner tube is
somewhat set back relative to the opening of the outer tube (Ann.
N.Y. Acad. Sc., Vol. 87, (1960), pages 658 to 668).
These known measuring arrangements are complex. In addition, the
liquid medium is returned to the sampling point and in some
instances so is the infusion solution. This permits substances
which have dissolved from membranes of the sensors to get to the
sampling. Additional harm can result if the membranes are not
sterilized.
SUMMARY OF THE INVENTION
The present invention obviates the above described deficiencies in
known measuring arrangements. The apparatus may include:
(a) a catheter having a plurality of lumens, each of said lumens
having a common opening to the liquid medium;
(b) means, coupled to a first one of said plurality of lumens, for
providing a reversible flow of an infusion solution, at said
opening, to and from said opening;
(c) a measuring canal coupled to a second one said plurality of
lumens;
(d) means for providing an outflow through said measuring canal at
a predetermined velocity;
(e) at least a first sensor and a second sensor, said measuring
canal connecting said first sensor and said second sensor and,
(f) wherein the size of the measuring canal is chosen so that
during a first time interval said first sensor is adjacent to the
infusion solution at the same time that said second sensor is
adjacent to said liquid medium and during a second time interval
said first sensor is adjacent to said liquid medium at the same
time said second sensor is adjacent to said infusion solution;
(g) means for measuring differences between outputs of said first
sensor and said second sensor.
In an embodiment of the apparatus of the present invention, an
infusion solution is fed to a measuring arrangement via a catheter.
The apparatus removes the necessity for a separate bridge
electrolyte solution as well as an electro-chemical reference
electrode with a diaphragm that is prone to contamination. All
sensors of the arrangement are subjected in the time average to the
same solutions; thus an ideal drift compensation is assured.
Although the two sensors in this arrangement serve alternatingly as
both a measuring sensor and a reference sensor, the designations
measuring sensor and reference sensor are retained in the following
description.
ChemFETs can preferably be provided as measuring and reference
sensors. The measuring and reference sensors are provided with the
same membranes. The measuring channel between the two ChemFETs can
be designed with a cover strip which may act as a heat exchanger.
For instance, sufficient heat transfer to the solution being
analyzed can be assured by a meander-shape or serpentine shape of
the measuring channel which can be preferably designed as a groove
in the cover strip.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows an overall picture of measuring apparatus according to
the present invention in a top view.
FIG. 2 illustrates a cross section of an element of the apparatus
of FIG. 1.
FIGS. 3 and 4 illustrate an advantageous operating method for the
apparatus of FIG. 1.
FIG. 5 illustrates an alternate embodiment for the catheter
illustrated in FIG. 1.
DETAILED DESCRIPTION
For purposes of explanation of the arrangement according to FIG. 1
the liquid medium is assumed to be blood.
Blood as the liquid measuring medium 2 flows through the vein 3 of
a patient, not shown in the figure. A two-lumen catheter 4 with,
for instance, concentrically arranged lumens is introduced into the
blood stream. The outer lumen 5, is connected via an infusion hose
14 and a device for reversing the direction of flow through hose
14, such as a reversible pump 15, to a container 40 holding an
infusion solution 16. The mouth 8 of the outer lumen 5 extends into
the blood stream. The inner lumen 6, whose mouth 7 is located
within the outer lumen 5, is connected via an infusion hose 9, a
measuring channel 12 and an infusion hose 17 to a device 18 for
producing a discharge of fluid at a predetermined velocity at
output 19. A hose pump can preferably be used as device 18. This
pump assures a constant measuring stream. A throttling valve is
also suitable, for use as the device 18. The measuring channel 12
connects two sensors which are designated in the following
description as the measuring sensor 10 and the reference sensor 11.
Both sensors serve alternatingly as a measuring sensor as well as a
reference sensor according to the arrangement of the present
invention. The sensors may be ChemFETS.
The measuring and reference sensors 10 and 11 can preferably be
integrated on a common chip 22 illustrated in FIG. 2. Evaluation
electronics 24 are associated with the sensors and are disposed on
the common chip 22. Optionally, a temperature sensor 26 can be
associated with the common chip 22 as well, preferably forming a
structural unit. The temperature sensor can be integrated on this
common chip 22. Thereby, a very compact design of a sensor block 20
is obtained. The overall dimension of the block 20 does not
substantially exceed about 10 mm and can be, in particular, less
than 10 mm. The block 20 can preferably form a common structural
unit with the catheter 4. An electrical solution contact 30 is
included in the measuring arrangement. The solution contact 30
makes contact with the infusion solution 16 which serves at the
same time as the reference and flushing solution. This solution
contact 30 can be arranged in the flow canal 9 or the flow canal 17
or in the measuring canal 12 between the two sensors 10 and 11.
Preferably the solution contact 30 is disposed in measuring canal
12 in the proximity of the reference sensor 11. The solution
contact 30 electrically connects either the liquid medium to be
analyzed 2 or the infusion solution 16 to the electrical reference
null point of the electronic evaluation circuitry 24.
The liquid medium 2 drawn from the patient, as well as the infusion
solution 16 drawn from the container 40 leave or are ejected from
the measuring apparatus at the output 19.
In one embodiment of the measuring apparatus according to FIG. 1, a
squeezing valve can also be provided in the catheter opening 8 for
reversing a direction of flow.
According to FIG. 2, the sensor block 20 can include a base plate
21 upon Which is disposed the common chip 22 which can preferably
consist of silicon. As stated above the common chip 22 may include
the electronic evaluation circuitry 24 as well as measuring sensor
10 and the reference sensor 11 which are integrated circuits of the
common chip 22. The sensor block 20 is covered by a cover strip 25.
The measuring canal 12 may be integrated with the cover strip 25 in
the form of a groove in the strip 25. The groove that forms the
measuring canal 12 may have a meandering or serpentining shape.
In a special embodiment, the cover strip 25 can further include a
heating device of FIG. 2. The heating device can act to thermally
stabilize the liquid medium under analysis 2 and the infusion
solution 16 while they are present in the measuring canal 12. For
this purpose, for instance, the heating device 26 can be a
semiconductor heating resistor, or a metal resistance heater. In an
embodiment utilizing the heating device, the measuring arrangement
is heated to the body temperature of the patient so that a
numerical pH value correction becomes unnecessary, whereas such
correction is necessary when the liquid medium under analysis cools
off from the body temperature to the room temperature when a
heating apparatus is not used. A correction that can be of an order
of magnitude of the measured value may be necessary if the liquid
medium is allowed to cool.
The operation of the arrangement illustrated in FIGS. 1 to 4 will
now be described.
The infusion solution 16, preferably a physiological electrolyte
solution and in particular, a Ringer solution, is first pumped by
means of the reversible pump 15 from the container 40 through the
infusion hose 14 into the outer lumen 5 of the catheter 4 toward
the blood circulation of the patient. At the same time, part of
this infusion solution 16 is drawn up toward the measuring sensor
10 through the opening 7 of the inner lumen 6 by the operation of
device 18.
If the operation of pump 15 is reversed no longer forcing infusion
solution to the opening of lumen 5, solution to be analyzed, blood,
2 is drawn through the opening 7 of the inner lumen 6 and flows
into the inner lumen 6 toward sensor 10. As soon as a predetermined
quantity of the solution to be analyzed 2 has flown into the inner
lumen 6, the pump 15 is reversed again.
In the rhythm of reversing the pump 15, a sequence of equal volumes
of the liquid medium to be analyzed 2 and the infusion solution 16
are alternately drawn toward the sensors 10 and 11. The size of the
volume parts of the two solutions in the measuring channel 12,
dependent upon the size of the measuring channel 12, is chosen so
that, as illustrated in FIG. 3, in a first time interval one
sensor, for instance, the reference sensor 11 is adjacent to the
infusion solution 16, while the other sensor, for instance, the
measuring sensor 10 is adjacent to the solution to be analyzed 2.
Similarly, in a second time interval, if the reference sensor 11 is
adjacent to the solution to be analyzed 2, the measuring sensor 10
is adjacent to the infusion solution 16. In this second time
interval the reference sensor 11 actually operates as a measuring
sensor and the measuring sensor 10 actually operates as a reference
sensor. Each sensor therefore serves alternatingly as a measuring
sensor and as a reference sensor.
In a measurement With the electronic evaluation circuitry 24, which
is shown for simplification in FIG. 3 as a measuring instrument,
one obtains a potential difference between a measuring potential
.phi..sub.M and a calibrating potential .phi..sub.E whereby:
A subsequent measurement according to FIG. 4 results in a potential
difference
In the present invention therefore .DELTA..phi..sub.1
=.DELTA..phi..sub.2
In the embodiment illustrated in FIG. 1, a catheter is shown in
which one lumen 5 is concentrically surrounded by a second lumen 6.
However, it is possible to utilize two or more separate lumens
arranged side by side with a common opening to the medium to be
analyzed or a plurality of concentric lumens as illustrated in FIG.
5. The outer lumen can further contain additional separate lumens
e.g. lumen 5' which may each be connected to different infusion
solutions 16' by flow reversing means 15'. One of the lumens may be
dedicated to the measurement of blood pressure.
In addition to the arrangement illustrated in FIGS. 3 and 4, it may
be desirable to perform a calibration again after each measurement
of the liquid medium to be analyzed. In such a case the rhythm of
the reversible pump 15 is adjusted to assure that infusion solution
16 is coupled to both of the sensors 10 and 11 simultaneously after
each measurement. This repetitive recalibration mode of operation
reduces to one half the amount of contact over time between the
sensors and the solution to be analyzed 2 compared to a system
without repetitive recalibration, thus, the danger of
contamination, for instance, a deposition of proteins on the
membranes of the respective sensors, is accordingly slight.
As described above the arrangement of the present invention can be
used for the examination of a liquid measuring medium for blood
analysis. However, the arrangement can also be used advantageously
in other technical fields, for instance, in biotechnology for
process control, in regulation in a bioreactor, and in the
continuous recording of pH values and of the concentration of
harmful ions in water.
* * * * *